Genetics and Heart Health After Cancer Therapy (Gene-HEART)

The overall objective of this study is to use patient-centered in vitro and in vivo models to answer the fundamental question of whether or not pathogenic mutations in BRCA1/2 result in an increased risk of CV disease

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Breast Cancer; Hereditary Breast/Ovarian Cancer (brca1, brca2); Drug-Induced Cardiomyopathy
• Intervention / Treatment: Diagnostic test: echocardiography; Other: Cardiopulmonary Exercise Testing; Other: Blood Collection

• Study Type: Observational
• Enrollment (Actual): 79

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Initial diagnosis of Breast Cancer in 2005 or later BRCA testing documenting either germline mutation in BRCA1/BRCA2 or no mutation in BRCA1/2.

Description

Inclusion Criteria

• ≥18 years of age
• Initial diagnosis of Breast Cancer in 2005 or later

• Documented BRCA testing (results from a local laboratory are acceptable) showing

  • confirmation of a germline mutation in BRCA1 or BRCA2 that is predicted or suspected to be deleterious OR
  • confirmation that no mutation was detected in BRCA1 or BRCA2
• Non-carriers will have been treated with an anthracycline-based chemotherapy regimen; carriers may or may not have been treated with an anthracycline-based chemotherapy regimen.
• Approximately at least 12 months from initiation of adjuvant treatment or neo-adjuvant chemotherapy
• Able to provide informed consent

Exclusion Criteria

• Stage IV Breast Cancer
• Genetic testing confirming a variant of unknown significance (VUS) or benign polymorphism in BRCA1 or BRCA2

• V02 Testing contraindicated for any reason, including:

  • Myocardial infarction (within past 3 months)
  • High-risk unstable angina;
  • High-risk or uncontrolled cardiac arrhythmias;
  • Symptomatic severe aortic stenosis;
  • Uncontrolled symptomatic heart failure;
  • Acute pulmonary embolus or pulmonary infarction;
  • Acute myocarditis or pericarditis;
  • Acute aortic dissection;
  • Coronary revascularization procedure within the past three months;
  • Uncontrolled hypertension, defined as systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 100mmHg;
  • Clinically significant valvular heart disease (severe stenosis or regurgitation);
  • Known aortic aneurysm; or
  • Any other condition which, in the opinion of the investigator, may impede testing of the study hypothesis or make it unsafe to engage in the V02 test
• Women who are pregnant
• Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Subjects with genetic testing confirming deleterious mutations in BRCA1 or BRCA2 whose prior treatment for breast cancer includes anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.	Diagnostic test: echocardiography; Resting echocardiograms (Vivid E9 or E95, GE Healthcare) with conventional measures of systolic and diastolic function, in conjunction with posthoc quantitation of novel measures of strain and strain rate will be obtained at each study time point.; Other: Cardiopulmonary Exercise Testing; A cardiopulmonary exercise test (CPET, also called V02 test) will be completed at each study time point utilizing a standard clinical protocol, on either a stationary bike or treadmill. The purpose of this test is to estimate maximal oxygen consumption (V02 max) as in index of cardiopulmonary fitness. Resting ECG, heart rate, and BP will be obtained prior to beginning the test, during each stage of the test and for 5 minutes after the test is stopped.; Other: Blood Collection; We will obtain blood samples (approximately 16mL) at baseline and (approximately 12mL) at each follow-up visit. Typically these will be drawn via peripheral venipuncture, however if patients have a port-a-cath in place, blood may be drawn from the port instead.
Group 2; Subjects with genetic testing confirming deleterious mutations in BRCA1 or BRCA2 whose prior treatment for breast cancer does not include anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.	Diagnostic test: echocardiography; Resting echocardiograms (Vivid E9 or E95, GE Healthcare) with conventional measures of systolic and diastolic function, in conjunction with posthoc quantitation of novel measures of strain and strain rate will be obtained at each study time point.; Other: Cardiopulmonary Exercise Testing; A cardiopulmonary exercise test (CPET, also called V02 test) will be completed at each study time point utilizing a standard clinical protocol, on either a stationary bike or treadmill. The purpose of this test is to estimate maximal oxygen consumption (V02 max) as in index of cardiopulmonary fitness. Resting ECG, heart rate, and BP will be obtained prior to beginning the test, during each stage of the test and for 5 minutes after the test is stopped.; Other: Blood Collection; We will obtain blood samples (approximately 16mL) at baseline and (approximately 12mL) at each follow-up visit. Typically these will be drawn via peripheral venipuncture, however if patients have a port-a-cath in place, blood may be drawn from the port instead.
Group 3; Subjects with genetic testing confirming no mutation in BRCA1 or BRCA2 whose prior treatment for breast cancer includes anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.	Diagnostic test: echocardiography; Resting echocardiograms (Vivid E9 or E95, GE Healthcare) with conventional measures of systolic and diastolic function, in conjunction with posthoc quantitation of novel measures of strain and strain rate will be obtained at each study time point.; Other: Cardiopulmonary Exercise Testing; A cardiopulmonary exercise test (CPET, also called V02 test) will be completed at each study time point utilizing a standard clinical protocol, on either a stationary bike or treadmill. The purpose of this test is to estimate maximal oxygen consumption (V02 max) as in index of cardiopulmonary fitness. Resting ECG, heart rate, and BP will be obtained prior to beginning the test, during each stage of the test and for 5 minutes after the test is stopped.; Other: Blood Collection; We will obtain blood samples (approximately 16mL) at baseline and (approximately 12mL) at each follow-up visit. Typically these will be drawn via peripheral venipuncture, however if patients have a port-a-cath in place, blood may be drawn from the port instead.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Left Ventricular Ejection Fraction	6 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 5, 2017
• Primary Completion (ACTUAL): May 31, 2022
• Study Completion (ACTUAL): May 31, 2022

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (ACTUAL): April 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Cardio-oncology
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies
• Other Study ID Numbers: UPCC 13117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No